Deletion of Pnpla2 Causes Malformation and Malperformance of Mouse Photoreceptors

Photoreceptor cells express the patatin-like phospholipase domain-containing 2 (PNPLA2) gene that codes for pigment epithelium-derived factor receptor (PEDF-R). PEDF-R exhibits phospholipase activity that mediates the neurotrophic action of its ligand PEDF. Because phospholipids are the most abundant lipid class in the retina, we investigated the role of PNPLA2 in photoreceptors by generating CRISPR Pnpla2 knockout mouse lines. We aim to characterize one of the two lines of mice generated with global Pnpla2 gene deletion. The retinas of Pnpla2^-/- mice had undetectable Pnpla2 gene expression, shorter retina and ONL heights, and photoreceptor deformities with loss of rhodopsin and opsin relative to controls. Furthermore, Pnpla2 deletion compromised photoreceptor function in vivo. In conclusion, ablation of the Pnpla2 gene in mice caused malformation and malperformance of photoreceptors, identifying PEDF-R as an important component for photoreceptor structure and function.